- Quercetin-3-oleoyl derivatives as new GPR40 agonists: Molecular docking studies and functional evaluation
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The G-protein-coupled receptor 40 (GPR40)is an attractive molecular target for the treatment of type 2 diabetes mellitus. Previously, based on the natural oleic acid substrate, an exogenous ligand for this receptor, named AV1, was synthesized. In this context, here we validated the activity of AV1 as a full agonist, while the corresponding catechol analogue, named AV2, was investigated for the first time. The ligand-protein interaction between this new molecule and the receptor was highlighted in the lower portion of the GPR40 groove that generally accommodates DC260126. The functional assays performed have demonstrated that AV2 is a suitable GPR40 partial agonist, showing a therapeutic potential and representing a useful tool in the management of type 2 diabetes.
- Carullo, Gabriele,Perri, Mariarita,Manetti, Fabrizio,Aiello, Francesca,Caroleo, Maria Cristina,Cione, Erika
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Read Online
- Synthesis, antiproliferative activity and radical scavenging ability of 5-o-acyl derivatives of quercetin
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Quercetin is a flavonoid that is found in many plant materials, including commonly eaten fruits and vegetables. The compound is well known for its wide range of biological activities. In this study, 5-O-acyl derivatives of quercetin were synthesised and a
- Barker, David,Fedrizzi, Bruno,Leung, Euphemia,Lo, Stephen
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Read Online
- New lipophenols prevent carbonyl and oxidative stresses involved in macular degeneration
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Dry age-related macular degeneration and Stargardt disease undergo a known toxic mechanism caused by carbonyl and oxidative stresses (COS). This is responsible for accumulation in the retinal pigment epithelium (RPE) of A2E, a main toxic pyridinium bis-retinoid lipofuscin component. Previous studies have shown that carbonyl stress in retinal cells could be reduced by an alkyl-phloroglucinol-DHA conjugate (lipophenol). Here, we performed a rational design of different families of lipophenols to conserve anti-carbonyl stress activities and improve antioxidant properties. Five synthetic pathways leading to alkyl-(poly)phenol derivatives, with phloroglucinol, resveratrol, catechin and quercetin as the main backbone, linked to poly-unsaturated fatty acid, are presented. These lipophenols were evaluated in ARPE-19 cell line for their anti-COS properties and a structure-activity relationship study is proposed. Protection of ARPE-19 cells against A2E toxicity was assessed for the four best candidates. Finally, interesting anti-COS properties of the most promising quercetin lipophenol were confirmed in primary RPE cells.
- Moine, Espérance,Boukhallat, Manel,Cia, David,Jacquemot, Nathalie,Guillou, Laurent,Durand, Thierry,Vercauteren, Joseph,Brabet, Philippe,Crauste, Céline
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p. 367 - 382
(2020/11/13)
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- QUERCETIN DERIVATIVE, PHARMACEUTICAL COMPOSITION FOR PREVENTING OR TREATING CANCER COMPRISING THE SAME, AND METHOD FOR SYNTHESIZING THE SAME
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The present invention relates to a novel quercetin derivative in which a 4′-hydroxy group of quercetin is substituted and which has excellent stability, to a pharmaceutical composition for preventing or treating cancer comprising the same, and to a synthe
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Paragraph 0122-0130
(2021/01/29)
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- Synthesis, characterization and antioxidant activity of quercetin derivatives
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A series of quercetin derivatives were synthesized via Williamson etherification, Steglich esterification or Koenigs–Knorr glycosylation reaction at 3 and 7 position hydroxyl groups selectively. The structures of the synthesized compounds were characteriz
- Sun, Lei,Lu, Bo,Liu, Yandan,Wang, Qian,Li, Gao,Zhao, Longxuan,Zhao, Chunhui
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supporting information
p. 2944 - 2953
(2021/08/25)
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- LIPOPHENOLIC FLAVONOID DERIVATIVES USEFUL TO REDUCE CARBONYL AND OXIDATIVE STRESSES (COS)
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The invention relates to compound of formula (I): in particular flavonoid derivatives (quercetin and catechin derivatives), for use in the prevention and/or the treatment of a disease or disorder involving both carbonyl and oxidative stresses.
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Paragraph 0114
(2020/02/04)
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- AMYLASE INHIBITOR COMPOUNDS, METHODS OF THEIR USE AND COMPOSITIONS THEREOF
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There are provided compounds of Formula I: various compositions thereof and methods for their use in the inhibition of α-amylase.
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Paragraph 0110
(2020/04/09)
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- Synthesis of Rhamnazin and Ombuin as methylated metabolites of quercetin
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The methylated metabolites of quercetin, rhamnazin and ombuin are highly likely to develop as anticancer and anti-inflammatory agents. In this study, we synthesized rhamnazin through selective methylation of quercetin hydroxyl group, which has not been reported so far. In addition, a new synthetic method was developed to correct the problems of previous synthetic method of ombuin, one of the methylated metabolites of quercetin.
- Jang, Jongyun,Kang, Dong Wook
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- Regiospecific synthesis of three quercetin O-β-glucosides of N-acetylglucosamine
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The regiospecific synthesis of three quercetin O-β-glucosides of N-acetylglucosamine has been achieved in good yield. Selective di- and tri-O-benzylation of quercetin followed by O-glycosylation with 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-α-d-glucopyranosyl chloride under phase-transfer catalysis conditions yielded, after deacetylation and debenzylation, 3-, 3′- and 4′-glycosylated quercetin.
- Cao, Zhiling,Chen, Jing,Zhu, Dandan,Yang, Zongnan,Teng, Wenqi,Liu, Gaofeng,Liu, Bing,Tao, Chuanzhou
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p. 189 - 193
(2018/05/26)
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- Quercetin derivative and its preparation method and application
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The invention discloses a quercetin derivative and a preparation method and application thereof. The preparation method comprises the following steps: firstly using dichlorodiphenylmethane to protect quercetin o-diphenol hydroxyl, combining a benzyl protection group to obtain the selectively protected quercetin derivative, and then independently reacting with dimethyl sulfate, diethyl sulfate, allyl bromide, paratoluensulfonyl chloride and acetic anhydride respectively to generate corresponding quercetin derivatives. All of the prepared derivative compounds have NRK-49F proliferation activity inhibition superior to that of quercetin. The quercetin derivatives 20a-1, 14a-1 and 23d-1 compositely replaced by methyl and p-tosyl have higher inhibition NRK-49F proliferation activity, and the inhibition ratio respectively reaches 86.33%, 78.04% and 75.91%. Thus, the currently obtained quercetin derivative compounds have obvious inhibition effect on kidney fibroblast NRK-49F proliferation.
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Paragraph 0032
(2018/01/19)
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- Quercetin derivatives as novel antihypertensive agents: Synthesis and physiological characterization
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The antihypertensive flavonol quercetin (Q1) is endowed with a cardioprotective effect against myocardial ischemic damage. Q1 inhibits angiotensin converting enzyme activity, improves vascular relaxation, and decreases oxidative stress and gene expression. However, the clinical application of this flavonol is limited by its poor bioavailability and low stability in aqueous medium. In the aim to overcome these drawbacks and preserve the cardioprotective effects of quercetin, the present study reports on the preparation of five different Q1 analogs, in which all OH groups were replaced by hydrophobic functional moieties. Q1 derivatives have been synthesized by optimizing previously reported procedures and analyzed by spectroscopic analysis. The cardiovascular properties of the obtained compounds were also investigated in order to evaluate whether chemical modification affects their biological efficacy. The interaction with β-adrenergic receptors was evaluated by molecular docking and the cardiovascular efficacy was investigated on the ex vivo Langendorff perfused rat heart. Furthermore, the bioavailability and the antihypertensive properties of the most active derivative were evaluated by in vitro studies and in vivo administration (1 month) on spontaneously hypertensive rats (SHRs), respectively. Among all studied Q1 derivatives, only the ethyl derivative reduced left ventricular pressure (at 10- 8 M ÷ 10- 6 M doses) and improved relaxation and coronary dilation. NOSs inhibition by L-NAME abolished inotropism, lusitropism and coronary effects. Chronic administration of high doses of this compound on SHR reduced systolic and diastolic pressure. Differently, the acetyl derivative induced negative inotropism and lusitropism (at 10- 10 M and 10- 8 ÷ 10- 6 M doses), without affecting coronary pressure. Accordingly, docking studies suggested that these compounds bind both β1/β2-adrenergic receptors. Taking into consideration all the obtained results, the replacement of OH with ethyl groups seems to improve Q1 bioavailability and stability; therefore, the ethyl derivative could represent a good candidate for clinical use in hypertension.
- Grande, Fedora,Parisi, Ortensia I.,Mordocco, Roberta A.,Rocca, Carmine,Puoci, Francesco,Scrivano, Luca,Quintieri, Anna M.,Cantafio, Patrizia,Ferla, Salvatore,Brancale, Andrea,Saturnino, Carmela,Cerra, Maria C.,Sinicropi, Maria S.,Angelone, Tommaso
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p. 161 - 170
(2015/12/11)
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- Biological evaluation and SAR analysis of O-methylated analogs of quercetin as inhibitors of cancer cell proliferation
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Preclinical Research Using a high-throughout screening approach, the anticancer activities of 16 O-methylated (OMe) analogs of quercetin were assessed. The structure-activity relationships showed that OMe moieties at the 4′ and/or 7 positions were important for maintaining inhibitory activities against the 16 cancer cell lines. Furthermore, when the OH groups at the 3′ and 4′ positions were both replaced by OMe moieties, anticancer activity was enhanced.
- Shi, Zhi-Hao,Li, Nian-Guang,Tang, Yu-Ping,Shi, Qian-Ping,Tang, Hao,Li, Wei,Zhang, Xu,Fu, Hai-An,Duan, Jin-Ao
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p. 455 - 462
(2015/04/14)
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- Water-soluble and cleavable quercetin-amino acid conjugates as safe modulators for P-glycoprotein-based multidrug resistance
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Quercetin-amino acid conjugates with alanine or glutamic acid moiety attached at 7-O and/or 3-O position of quercetin were prepared, and their multidrug resistance (MDR)-modulatory effects were evaluated. A quercetin-glutamic acid conjugate, 7-O-Glu-Q (3a
- Kim, Mi Kyoung,Choo, Hyunah,Chong, Youhoon
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p. 7216 - 7233
(2015/01/08)
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- Synthesis and bioactivity of quercetin aspirinates
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Hybrids of some natural compounds are promising to obtain new leads with good biological activities for drug discovery. Three quercetin aspirinates were synthesized by esterification of the 3-and 7-hydroxyl groups of quercetin with aspirin. Biological act
- Lu, Chenjuan,Huang, Feng,Li, Zexin,Ma, Jinshuo,Li, Huanhuan,Fang, Lizhen
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p. 518 - 520
(2014/03/21)
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- Design and discovery of flavonoid-based HIV-1 integrase inhibitors targeting both the active site and the interaction with LEDGF/p75
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HIV integrase (IN) is an essential enzyme for the viral replication. Currently, three IN inhibitors have been approved for treating HIV-1 infection. All three drugs selectively inhibit the strand transfer reaction by chelating a divalent metal ion in the
- Li, Bo-Wen,Zhang, Feng-Hua,Serrao, Erik,Chen, Huan,Sanchez, Tino W.,Yang, Liu-Meng,Neamati, Nouri,Zheng, Yong-Tang,Wang, Hui,Long, Ya-Qiu
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p. 3146 - 3158
(2014/06/09)
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- Quercetin-POC conjugates: Differential stability and bioactivity profiles between breast cancer (MCF-7) and colorectal carcinoma (HCT116) cell lines
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In the course of our ongoing efforts to develop novel quercetin conjugates with enhanced stability profiles, we introduced an isopropyloxycarbonylmethoxy (POC) group to 7-OH and/or 3-OH of quercetin and prepared three novel quercetin conjugates. The querc
- Cho, Suh Young,Kim, Mi Kyoung,Park, Kwang-Su,Choo, Hyunah,Chong, Youhoon
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p. 1671 - 1679
(2013/05/08)
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- Metabolism-based synthesis, biologic evaluation and SARs analysis of O-methylated analogs of quercetin as thrombin inhibitors
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In blood, quercetin is mainly found in metabolized forms. In order to study the activities of these quercetin metabolites in cardiovascular disease, 17 methylquercetin derivatives were synthesized based on metabolism in vivo, their thrombin inhibition activity were evaluated through the analyzation of prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT) and fibrinogen (FIB). The results showed that 6 methylquercetin derivatives had stronger inhibitory activities than that of quercetin. Preliminary SARs analysis showed that hydroxyl groups at C-3′ and C-4′ position in the B-ring and hydroxyl group at C-3 position in the C-ring played key roles in the thrombin inhibitory activity. The findings of this study would provide information for the exploitation and utilization of quercetin as thrombin inhibitor for thrombotic disease treatment.
- Shi, Zhi-Hao,Li, Nian-Guang,Tang, Yu-Ping,Wei-Li,Lian-Yin,Yang, Jian-Ping,Hao-Tang,Duan, Jin-Ao
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experimental part
p. 210 - 222
(2012/09/07)
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- NOVEL FLAVANONE DERIVATIVE
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Provided is a novel antimicrobial agent. More specifically, provided is a novel antimicrobial agent capable of effectively acting on various resistant bacteria such as VSSA, MRSA, VISA, VRE, and VRSA. A novel flavanone derivative having a six-membered monosaccharide derivative, specifically, a glucose derivative or a galactose derivative is capable of effectively acting on the bacteria. More specifically, a compound represented by the general formula (I) is capable of effectively acting on the bacteria. (In the formula: X represents a six-membered monosaccharide derivative; and Y is substituted by a hydroxyl group.)
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Page/Page column 13
(2012/06/18)
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- Regiospecific synthesis of quercetin O-β-d-glucosylated and O-β-d-glucuronidated isomers
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Quercetin, the polyphenolic compound, which has the highest daily intake, is well known for its protective effects against aging diseases and has received a lot of attention for this reason. Both quercetin 3-O-β-d-glucuronide and quercetin 3′-O-β-d-glucuronide are human metabolites, which, together with their regioisomers, are required for biological as well as physical chemistry studies. We present here a novel synthetic route based on the sequential and selective protections of the hydroxyl functions of quercetin allowing selective glycosylation, followed by TEMPO-mediated oxidation to the glucuronide. This methodology enabled us to synthesize the five O-β-d-glucosides and four O-β-d-glucuronides of quercetin, including the major human metabolite, quercetin 3-O-β-d-glucuronide.
- Kajjout, Mohammed,Rolando, Christian
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supporting information; experimental part
p. 4731 - 4741
(2011/07/08)
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- Enhanced stability and intracellular accumulation of quercetin by protection of the chemically or metabolically susceptible hydroxyl groups with a pivaloxymethyl (POM) promoiety
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In order to increase stability of quercetin, its metabolically and chemically susceptible hydroxyl groups 7-OH and 3-OH respectively were transiently blocked with a pivaloxymethyl (POM) promoiety to provide two novel quercetin conjugates [7-O-POM-Q (2), 3
- Kim, Mi Kyoung,Park, Kwang-Su,Lee, Chaewoon,Park, Hye Ri,Choo, Hyunah,Chong, Youhoon
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experimental part
p. 8597 - 8607
(2011/02/25)
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- Design, synthesis, and biological evaluation of a novel series of quercetin diacylglucosides as potent anti-MRSA and anti-VRE agents
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A series of novel quercetin diacylglucosides were designed and first synthesized by Steglich esterification on the basis of MRSA strains inhibiting natural compound A. The in vitro inhibition of different multi-drug resistant bacterial strains and Escherichia coli DNA gyrase B was investigated. In the series, compound 10h was up to 128-fold more potent against vancomycin-resistant enterococci and more effective than A, which represents a promising new candidate as a potent anti-MRSA and anti-VRE agent.
- Hossion, Abugafar M.L.,Otsuka, Nao,Kandahary, Rafiya K.,Tsuchiya, Tomofusa,Ogawa, Wakano,Iwado, Akimasa,Zamami, Yoshito,Sasaki, Kenji
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scheme or table
p. 5349 - 5352
(2010/10/18)
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- An efficient partial synthesis of 4'-O-methylquercetin via regioselective protection and alkylation of quercetin
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An efficient partial 5-step synthesis of 4'-O-methylquercetin from quercetin in 63% yield is reported. This strategy relies on the selective protection of the catechol group with dichlorodiphenylmethane in diphenyl ether as solvent and on the selective pr
- Li, Nian-Guang,Tang, Yu-Ping,Yang, Jian-Ping,Duan, Jin-Ao,Shi, Zhi-Hao
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experimental part
(2010/04/22)
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- ANTIOXIDANT FLAVONOID DERIVATIVES
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The present invention relates to antioxidant flavonoids, compositions containing such antioxidant flavonoids, methods for using such antioxidant flavonoids to treat, e.g., AMD, and methods for making such antioxidant flavonoids. Also provided are methods for ameliorating A2E photooxidation, especially in cells and mammals, particularly, humans.
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Page/Page column 39; 41; 42; 43; 44; 45
(2009/06/27)
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- Synthesis of β-sitosterol-quercetin dyads
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Synthesis of novel β-sitosterol-quercetin dyads 6 and 10 as serum cholesterol lowering agent is described. These compounds were prepared in good yields by the reaction of β-sitosterol and succinic anhydride, followed by the activation of the resulting aci
- Kim, Kwanghyun,Song, Yang-Heon
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body text
p. 405 - 408
(2010/03/04)
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- BENZOPYRANONE DERIVATIVES AND THEIR USE AS ANTI-CORONAVIRAL AGENTS
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The invention relates to pharmaceutical compositions comprising benzopyranone derivatives for the treatment of Severe Acute Respiratory Syndrome (SARS).
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Page/Page column 31
(2008/06/13)
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- Binding interaction of quercetin-3-β-galactoside and its synthetic derivatives with SARS-CoV 3CLpro: Structure-activity relationship studies reveal salient pharmacophore features
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The 3C-like protease (3CLpro) of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is one of the most promising targets for discovery of drugs against SARS, because of its critical role in the viral life cycle. In this study,
- Chen, Lili,Li, Jian,Luo, Cheng,Liu, Hong,Xu, Weijun,Chen, Gang,Liew, Oi Wah,Zhu, Weiliang,Puah, Chum Mok,Shen, Xu,Jiang, Hualiang
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p. 8295 - 8306
(2007/10/03)
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- Synthesis and biological evaluation of flavonoids as vasorelaxant agents
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Several 5,7-dihydroxyflavone and quercetin 3-O-glycosides have been synthesized and evaluated for vasorelaxant activity. A logP-activity relationship amongst flavonoids was suggested.
- Chen, Zhiwei,Hu, Yongzhou,Wu, Haohao,Jiang, Huidi
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p. 3949 - 3952
(2007/10/03)
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- Hemisynthesis of all the O-monomethylated analogues of quercetin including the major metabolites, through selective protection of phenolic functions
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A new methodology for the hemisynthesis of all the five O-monomethylated analogues of quercetin (3′-O-methylquercetin (isorhamnetin), 4′-O-methylquercetin (tamarixetin), 3-O-methylquercetin, 5-O-methylquercetin (azaleatin) and 7-O-methylquercetin (rhamnetin)) through sequential protection of the different phenolic functions of quercetin is reported.
- Bouktaib, Mohamed,Lebrun, Stéphane,Atmani, Aziz,Rolando, Christian
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p. 10001 - 10009
(2007/10/03)
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- Regio- and stereoselective synthesis of the major metabolite of quercetin, quercetin-3-O-β-D-glucuronide
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Protected quercetin was first transformed selectively in its 3-O-β-D-glucoside. Further protection of the remaining phenolic hydroxyl group allows a clean oxidation of the glucoside by TEMPO/NaOCl/NaBr under phase transfer conditions into the corresponding glucuronide which was cleanly deprotected to quercetin-3-O-β-D-glucuronide.
- Bouktaib, Mohamed,Atmani, Aziz,Rolando, Christian
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p. 6263 - 6266
(2007/10/03)
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- Quercetin (=2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-4H-1-benzopyran-4-one) Glycosides and Sulfates: Chemical Synthesis, Complexation, and Antioxidant Properties
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Glycosides, acylated glycosides, and sulfates of Quercetin (=3,3',4',5,7-pentahydroxyflavone; 1), which is, together with its derivatives, among the most common polyophenols found in plants and in the human diet, were prepared and quantitatively investiga
- Alluis, Bertrand,Dangles, Olivier
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p. 1133 - 1156
(2007/10/03)
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